PUBLIC ABSTRACT Opioid medication misuse and overdose have reached epidemic proportions in the US, costing an es- timated $56 billion annually. One greatly underutilized resource for intervention is community pharmacy. Community pharmacies are primary locations where patients fill opioid medications that are often diverted and misused. Pharmacists are ranked among the most trusted healthcare professionals in the nation and have ex- pressed great interest in helping patients who misuse opioid medications; however, these professionals also report a lack of training and resources necessary to effectively do so. Deploying readily scalable opioid misuse and overdose prevention interventions within community pharmacy settings potentially has the capacity to be applied in thousands of locations. The current small scale single-blinded randomized controlled study will build on our preliminary studies by manualizing and examining the feasibility, acceptability, and clinical effect for the Brief Intervention Medication Therapy Management (BI-MTM) model. BI-MTM is a multicomponent community pharmacy-based intervention. BI-MTM is designed to: (1) promote opioid medication regimen adherence, (2) reduce opioid medication misuse, (3) connect participants with patient navigation (a chronic condition care model) to increase self-management of health conditions that increase risk for misuse, and (4) provide nalox- one rescue training referrals. Patients will be screened across 14 months for opioid medication misuse in an urban community pharmacy affiliated with a major medical system. Patients positive for misuse will be random- ly assigned to BI-MTM (n=23) or Standard Medication Counseling (n=23). Standard Medication Counseling is the Centers for Medicaid and Medicare Services requirement for pharmacists in the US wherein pharmacy pa- tients filling prescriptions receive information and opt-in counseling. This study will demonstrate feasibility and acceptability of BI-MTM for community pharmacy patients who misuse their opioid medications for future inter- vention implementation in a fully powered randomized trial. This study will also generate preliminary data re- garding opioid medication misuse elimination and increases in participant self-management activation for comorbid health conditions that increase risk for misuse.